Chemokines are produced by a variety of cell types in response to signals associated with host defense and wound repair. These proteins function by binding specific receptors on leukocytes thereby activating these cells in order to initiate the inflammatory response and vascularization in affected tissues. However, unabated production of chemokines is associated with a variety of inflammatory diseases and cancers. Over 50 human chemokines have been identified and divided into two major families based on amino acid sequences and leukocyte activation specificities. Specificity is tightly controlled in chemokine/receptor interactions and only one receptor, the promiscuous erythrocyte chemokine receptor, has been shown to tightly bind members of both chemokine families. Experiments suggest that the erythrocyte receptor and the family specific receptors bind chemokines using similar chemokine interfaces. This implies that chemokine binding to the erythrocyte receptor retains some of the interactions used in the family specific receptors and makes use of additional interactions which can be shared between the two chemokine families. In vivo experiments have localized chemokine binding to the N-terminal extracellular domain of the erythrocyte receptor. I propose to clone this domain of the receptor, structurally characterize its interactions with a member of each chemokine family and determine the solution structure of it in complex with a chemokine by high resolution NMR. This data will increase our understanding of chemokine/receptor binding specificity and will provide a template for future functional studies and the development of therapeutics aimed at modulating chemokine activity.